Drug Receptor Interactions in Antimicrobial Chemotherapy: "Symposium, Vienna, September 4-6, 1974"

The concept of chemotherapy as originated by Paul Ehrlich is based on the premise that antiparasitic drugs must have two properties: they must first bind to specific structures of the parasite which Ehrlich called chemoreceptors. Subsequent to their attachment to the chemoreceptor and by virtue of this binding they must possess the capacity to kill the parasite. Since the host which is to be cured of an invading parasite also contains a large number of chemoreceptors, that have the potential to bind toxic compounds, the task of the chemo­ therapist is to identify chemoreceptors of the parasite which are . not represented in the host and to design drugs which bind selectively to them~ In this context, Ehrlich called· for "the complete and exhaustive knowledge of all the different chemoreceptors of a certain parasite" as a "sine qua non for success in chemotherapy". Paradoxically and in spite of the fact that chemotherapy has become a very advanced and successful therapeutic discipline, few of its tri­ umphs have been achieved by following Ehrlich's original precepts. On the contrary, in the overwhelming majority of cases, effective drugs have been discovered without any knowledge of their chemoreceptors, and these drugs themselves have conversely been used as tools to study the nature of the chemoreceptors involved. In other words: chemother­ apy, notably antibacterial chemotherapy, has been successful without ever living up to the fundamental standards put forward by Paul Ehr­ lich. Front Matter....Pages I-VIII Front Matter....Pages 1-1 Structure-Activity Rules and the Receptor Hypothesis....Pages 3-14 Strategy of Drug-Design....Pages 15-24 Physicochemical Factors in Drug-Receptor Interactions Demonstrated on the Example of the Sulfanilamides....Pages 25-43 Quantitative Structure-Activity Relationships in Drug-Design....Pages 45-56 Front Matter....Pages 57-57 The Ecological Significance of R Factor Activity....Pages 59-76 Structural Constraints in the Binding of Drugs to DNA....Pages 77-90 Molecular Aspects of the Biosynthesis of R Factor DNA....Pages 91-98 Elimination of Plasmidic Determinants by DNA-Complexing Compounds....Pages 99-113 Front Matter....Pages 115-115 Antibiotic Receptor-Sites in Escherichia coli Ribosomes....Pages 117-143 Altered Methylation of Ribosomal RNA in Erythromycin-Resistant Staphylococcus Aureus....Pages 145-155 Binding of Tetracyclines and Other Antibiotics to Ribosomes....Pages 157-165 Ribosomal Effects of Thiostrepton and Related Antibiotics....Pages 167-177 Studies on Active Sites of Ribosomes with Haloacetylated Antibiotic Analogs....Pages 179-190 Front Matter....Pages 191-191 Antibiotic Action on the Ribosomal Peptidyl Transferase Centre....Pages 193-216 Experiments on the Binding Sites and the Action of Some Antibiotics which Inhibit Ribosomal Functions....Pages 217-234 The Mode of Action of Pleuromutilin as Compared to Chloramphenicol....Pages 235-244 A Structural Model of the Chloramphenicol Receptor Site....Pages 245-266 Front Matter....Pages 267-267 Spin-Labelled Intermediates as Targets of Antibiotic Action in Peptidoglycan Synthesis....Pages 269-284 Enzyme Inhibitors as Antimicrobial Agents....Pages 285-293 Molecular Mechanism of Action of Rifamycins....Pages 295-300 Back Matter....Pages 301-314